Disseminated intravascular coagulation

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Disseminated intravascular coagulation or
Disseminated intravascular coagulopathy
Classification and external resources
ICD-10 D65.
ICD-9 286.6
DiseasesDB 3765
eMedicine med/577 emerg/150
MeSH [1]

Disseminated intravascular coagulation (DIC), also known as consumptive coagulopathy, is

a pathological activation of coagulation (blood clotting) mechanisms that happens in response to
a variety of diseases. As its name suggests, it leads to the formation of small blood clots inside
the blood vessels throughout the body.[1] As the small clots consume all the available coagulation
proteins and platelets, normal coagulation is disrupted and abnormal bleeding occurs from the
skin (e.g. from sites where blood samples were taken), the digestive tract, the respiratory tract
and surgical wounds. The small clots also disrupt normal blood flow to organs (such as the
kidneys), which may malfunction as a result.[2]

DIC can occur acutely but also on a slower, chronic basis, depending on the underlying problem.
[3]
It is common in the critically ill, and may participate in the development of multiple organ
failure, which may lead to death.[4]

Contents
[hide]

• 1 Epidemiology
• 2 Pathophysiology
• 3 Causes
• 4 Signs and symptoms
• 5 Diagnosis
• 6 Treatment
• 7 Prognosis
• 8 See also

• 9 References
 [edit] Epidemiology
About half of DIC cases result from complications of pregnancy, and about a third result from
carcinomatosis. All other causes make up the remaining sixth of cases.[3]

[edit] Pathophysiology
Under homeostatic conditions, the body is maintained in a finely tuned balance of coagulation
and fibrinolysis. The activation of the coagulation cascade yields thrombin that converts
fibrinogen to fibrin; the stable fibrin clot being the final product of hemostasis. The fibrinolytic
system then functions to break down fibrinogen and fibrin. Activation of the fibrinolytic system
generates plasmin (in the presence of thrombin), which is responsible for the lysis of fibrin clots.
The breakdown of fibrinogen and fibrin results in polypeptides called fibrin degradation products
(FDPs) or fibrin split products (FSPs). In a state of homeostasis, the presence of thrombin is
critical, as it is the central proteolytic enzyme of coagulation and is also necessary for the
breakdown of clots, or fibrinolysis.

In DIC, the processes of coagulation and fibrinolysis lose control, and the result is widespread
clotting with resultant bleeding. Regardless of the triggering event of DIC, once initiated, the
pathophysiology of DIC is similar in all conditions. One critical mediator of DIC is the release of
a transmembrane glycoprotein called tissue factor (TF). TF is present on the surface of many cell
types (including endothelial cells, macrophages, and monocytes) and is not normally in contact
with the general circulation, but is exposed to the circulation after vascular damage. For
example, TF is released in response to exposure to cytokines (particularly interleukin 1), tumor
necrosis factor, and endotoxin[5]. This plays a major role in the development of DIC in septic
conditions. TF is also abundant in tissues of the lungs, brain, and placenta. This helps to explain
why DIC readily develops in patients with extensive trauma. Upon activation, TF binds with
coagulation factors that then trigger both the intrinsic and the extrinsic pathways of coagulation.

The release of endotoxin is the mechanism by which Gram-negative sepsis provokes DIC. In
acute promyelocytic leukemia, treatment causes the destruction of leukemic granulocyte
precursors, resulting in the release of large amounts of proteolytic enzymes from their storage
granules, causing microvascular damage. Other malignancies may enhance the expression of
various oncogenes that result in the release of TF and plasminogen activator inhibitor-1 (PAI-1),
which prevents fibrinolysis.[6]

Excess circulating thrombin results from the excess activation of the coagulation cascade. The
excess thrombin cleaves fibrinogen, which ultimately leaves behind multiple fibrin clots in the
circulation. These excess clots trap platelets to become larger clots, which leads to microvascular
and macrovascular thrombosis. This lodging of clots in the microcirculation, in the large vessels,
and in the organs is what leads to the ischemia, impaired organ perfusion, and end-organ damage
that occurs with DIC.

Coagulation inhibitors are also consumed in this process. Decreased inhibitor levels will permit
more clotting so that a feedback system develops in which increased clotting leads to more
clotting. At the same time, thrombocytopenia occurs because of the entrapment and consumption
of platelets. Clotting factors are consumed in the development of multiple clots, which
contributes to the bleeding seen with DIC.

Simultaneously, excess circulating thrombin assists in the conversion of plasminogen to plasmin,

resulting in fibrinolysis. The breakdown of clots results in excess amounts of FDPs, which have
powerful anticoagulant properties, contributing to hemorrhage. The excess plasmin also activates
the complement and kinin systems. Activation of these systems leads to many of the clinical
symptoms that patients experiencing DIC exhibit, such as shock, hypotension, and increased
vascular permeability. The acute form of DIC is considered an extreme expression of the
intravascular coagulation process with a complete breakdown of the normal homeostatic
boundaries. DIC is associated with a poor prognosis and a high mortality rate.

[edit] Causes
DIC can occur in the following conditions:[3][4][7]

• Cancers of lung, pancreas, prostate and stomach

• Obstetric: abruptio placentae, retained dead fetus, pre-eclampsia, amniotic fluid
embolism
• Massive tissue injury: Trauma, burns, extensive surgery
• Infections: Gram-negative sepsis, Neisseria meningitidis, Streptococcus pneumoniae,
malaria, histoplasmosis, aspergillosis, Rocky mountain spotted fever
• Miscellaneous: Liver disease, snake bite, acute intravascular hemolysis, giant
hemangioma, shock, heat stroke, vasculitis, aortic aneurysm, Serotonin syndrome[8]

[edit] Signs and symptoms

The affected person is often acutely ill and shocked with widespread haemorrhage (common
bleeding sites are mouth, nose and venipuncture sites), extensive bruising, renal failure and
gangrene.[7][9] The onset of DIC can be fulminant, as in endotoxic shock or amnioitic fluid
embolism, or it may be insidious and chronic, as in cases of carcinomatosis or retention of dead
fetus.[3]

[edit] Diagnosis
Diagnosis is usually suggested by following conditions:[7]

• Severe cases with haemorrhage: The PT and APTT are usually very prolonged and the
fibrinogen level markedly reduced. High levels of fibrin degradation products, including
D-dimer, are found owing to the intense fibrinolytic activity stimulated by the presence of
fibrin in the circulation. There is severe thrombocytopenia. The blood film may show
fragmented red blood cells (schistocytes).
 • Mild cases without bleeding: There is increased synthesis of coagulation factors and
platelets. PT, APTT, and platelet counts are normal. fibrin degradation products are
raised.

Definitive diagnosis depends on the result of: [10]

• Thrombocytopenia
• Prolongation of prothrombin time and activated partial thromboplastin time
• A low fibrinogen concentration
• Increased levels of fibrin degradation products

[edit] Treatment
The only effective treatment is the reversal of the underlying cause. Anticoagulants are given
exceedingly rarely when thrombus formation is likely to lead to imminent death (such as in
coronary artery thrombosis or cerebrovascular thrombosis). Platelets may be transfused if counts
are less than 5,000-10,000/mm3 and massive hemorrhage is occurring, and fresh frozen plasma
may be administered in an attempt to replenish coagulation factors and anti-thrombotic factors,
although these are only temporizing measures and may result in the increased development of
thrombosis.

DIC results in lower fibrinogen levels (as it has all been converted to fibrin), and this can be
tested for in the hospital lab. A more specific test is for "fibrin split products" (FSPs) or "fibrin
degradation products" (FDPs) which are produced when fibrin undergoes degradation when
blood clots are dissolved by fibrinolysis.

In some situations, infusion with antithrombin may be necessary.

[edit] Prognosis
Prognosis varies depending on the underlying disorder. The prognosis for those with DIC,
regardless of cause, is often grim. The colloquial reference "death is coming," refers to the lack
of existing and alternative forms of available treatment options, and to an expected worsening
prognosis.[11]

Disseminated intravascular coagulation (DIC)

Images
Blood clot formation

Meningococcemia on the calves

Meningococcemia on the leg

Meningococcemia associated purpura

Blood clots

Read More
Blood clots

Sepsis

Transfusion reaction - hemolytic

Liver disease

Mesenteric venous thrombosis

Disseminated intravascular coagulation (DIC) is a serious disorder in which the proteins that
control blood clotting become abnormally active.

Causes

Normally, when you are injured, certain proteins in the blood become activated and travel to the
injury site to help stop bleeding. However, in persons with DIC, these proteins become
abnormally active.

Small blood clots form within the blood vessels. Some of these clots can clog up the vessels and
cut off blood supply to various organs such as the liver or kidney. These organs will then stop
functioning. Over time, the clotting proteins become "used up." When this happens, the person is
then at risk for serious bleeding from even a minor injury.

This disorder can result in clots or, more often, in bleeding. The bleeding can be severe.

Risk factors for DIC include:

• Blood transfusion reaction

• Cancer, including leukemia
• Infection in the blood by bacteria or fungus
• Pregnancy complications (such as retained placenta after delivery)
• Recent surgery or anesthesia
• Sepsis (an overwhelming infection)
• Severe liver disease
• Severe tissue injury (as in burns and head injury)

Symptoms

• Bleeding, possibly from multiple sites in the body

• Blood clots
• Drop in blood pressure
• Sudden bruising

Exams and Tests

The following tests may be done:

• Examination of a blood sample under a microscope

• Fibrin degradation products - high
• Partial thromboplastin time (PTT) - high
• Platelet count - low
• Prothrombin time (PT) - high
• Serum fibrinogen - low

Treatment

The goal is to determine and treat the underlying cause of DIC.

Blood clotting factors will be replaced with plasma transfusions. Heparin, a medication used to
prevent clotting, is sometimes used also.

Outlook (Prognosis)

The outcome depends on what is causing the disorder.

Possible Complications

• Lack of blood flow to arms, legs, or vital organs

• Severe bleeding
• Stroke

When to Contact a Medical Professional

Go to the emergency room or call 911 if you have bleeding that won't stop.

Prevention

Get prompt treatment for conditions known to bring on this disorder.

Alternative Names

Consumption coagulopathy

ntroduction
Background

Disseminated intravascular coagulation (DIC) is a complex systemic thrombohemorrhagic

disorder involving the generation of intravascular fibrin and the consumption of procoagulants
and platelets. The resultant clinical condition is characterized by intravascular coagulation and
hemorrhage.

The subcommittee on DIC of the International Society on Thrombosis and Haemostasis has
suggested the following definition for DIC: "An acquired syndrome characterized by the
intravascular activation of coagulation with loss of localization arising from different causes. It
can originate from and cause damage to the microvasculature, which if sufficiently severe, can
produce organ dysfunction."1

DIC is not an illness on its own but rather a complication or an effect of progression of other
illnesses and is estimated to be present in up to 1% of hospitalized patients.2

DIC is always secondary to an underlying disorder and is associated with a number of clinical
conditions (see List below), generally involving activation of systemic inflammation. DIC has
several consistent components including activation of intravascular coagulation, depletion of
clotting factors, and end-organ damage (see Components of DIC). DIC is most commonly
observed in severe sepsis and septic shock. Indeed the development and severity of DIC
correlates with mortality in severe sepsis.3,4 Although bacteremia, including both gram-positive
and gram-negative organisms, is most commonly associated with DIC, other organisms
including viruses, fungi, and parasites may cause DIC.

Trauma, especially neurotrauma, is also frequently associated with DIC. DIC is more frequently
observed in those patients with trauma who develop the systemic inflammatory response
syndrome.5 Evidence indicates that inflammatory cytokines play a central role in DIC in both
trauma patients and septic patients. In fact, systemic cytokine profiles in both septic patients and
trauma patients are nearly identical.6

Conditions associated with DIC include the following7 :

• Sepsis/severe infection
• Trauma (neurotrauma)
• Organ destruction
• Malignancy (solid and myeloproliferative malignancies)
• Severe transfusion reactions
• Rheumatologic illness
o Adult Stills disease
o Lupus
• Obstetric complications
o Amniotic fluid embolism
o Abruptio placentae
o Hemolysis, elevated liver enzymes, low platelets (HELLP)
syndrome/eclampsia
o Retained dead fetus syndrome
• Vascular abnormalities
o Kasabach-Merritt syndrome
o Large vascular aneurysms
• Severe hepatic failure
• Severe toxic reactions
o Envenomations
o Transfusion reactions
o Transplant rejection

Acute DIC versus chronic DIC

DIC exists in both acute and chronic forms. DIC develops acutely when sudden exposure of
blood to procoagulants occurs, including tissue factor (tissue thromboplastin), generating
intravascular coagulation. Compensatory hemostatic mechanisms are quickly overwhelmed, and,
as a consequence, a severe consumptive coagulopathy leading to hemorrhage
develops. Abnormalities of blood coagulation parameters are readily identified, and organ failure
frequently occurs in acute DIC.

In contrast, chronic DIC reflects a compensated state that develops when blood is continuously
or intermittently exposed to small amounts of tissue factor. Compensatory mechanisms in the
liver and bone marrow are not overwhelmed, and there may be little obvious clinical or
laboratory indication of the presence of DIC. Chronic DIC is more frequently observed in solid
tumors and in large aortic aneurysms.8

Pathophysiology
DIC is caused by widespread and ongoing activation of coagulation, leading to vascular or
microvascular fibrin deposition, thereby compromising an adequate blood supply to various
organs. Four different mechanisms are primarily responsible for the hematologic derangements
seen in DIC: increased thrombin generation, a suppression of anticoagulant pathways, impaired
fibrinolysis, and inflammatory activation.9 Activation of intravascular coagulation is mediated
almost entirely by the intrinsic clotting pathway.

Exposure to tissue factor in the circulation occurs via endothelial disruption, tissue damage, or
inflammatory or tumor cell expression of procoagulant molecules, including tissue factor. Tissue
factor activates coagulation by the intrinsic pathway involving factor VIIa. Factor VIIa has been
implicated as the central mediator of intravascular coagulation in sepsis. Blocking the factor VIIa
pathway in sepsis has been shown to prevent the development of DIC, whereas interrupting
alternative pathways did not demonstrate any effect on clotting.10,11 The tissue factor-VIIa
complex then serves to activate thrombin, which, in turn, cleaves fibrinogen to fibrin while
simultaneously causing platelet aggregation. Evidence suggests that the intrinsic (or contact)
pathway is also activated in DIC, while contributing more to hemodynamic instability and
hypotension than to activation of clotting.12

Thrombin generation is usually tightly regulated by multiple hemostatic mechanisms. However,

once intravascular coagulation commences, compensatory mechanisms are overwhelmed or
incapacitated. Antithrombin is one such mechanism responsible for regulating thrombin
levels. However, due to multiple factors, antithrombin activity is reduced in patients with
sepsis. First, antithrombin is continuously consumed by ongoing activation of
coagulation. Moreover, elastase produced by activated neutrophils degrades antithrombin as well
as other proteins. Further antithrombin is lost to capillary leakage. Lastly, production of
antithrombin is impaired secondary to liver damage resulting from under-perfusion and
microvascular coagulation.8,13 Decreased levels of antithrombin correlate well with elevated
mortality in patients with sepsis.4

Protein C, along with protein S, serves as an important anticoagulant compensatory mechanism.

Under normal conditions, protein C is activated by thrombin and is complexed on the endothelial
cell surface with thrombomodulin.8 Activated protein C combats coagulation via proteolytic
cleavage of factors Va and VIIIa. However, the cytokines (tumor necrosis factor α [TNF-α ],
interleukin 1 [IL-1]) produced in sepsis and other generalized inflammatory states largely
incapacitate the protein C pathway. Inflammatory cytokines down-regulate the expression of
thrombomodulin on the endothelial cell surface.14 Protein C levels are further reduced via
consumption, extravascular leakage, and reduced hepatic production and by a reduction in freely
circulating protein S.

Tissue factor pathway inhibitor (TFPI) is another anticoagulant mechanism that is disabled in
DIC. TFPI inhibits the tissue factor-VIIa complex. Although levels of TFPI are normal in
patients with sepsis, a relative insufficiency in DIC is evident. TFPI depletion in animal models
predisposes to DIC, and TFPI blocks the procoagulant effect of endotoxin in humans.15 The
intravascular fibrin produced by thrombin is normally eliminated via a process termed
fibrinolysis. The initial response to inflammation appears to be augmentation of fibrinolytic
action; however, this response soon reverses as inhibitors (plasminogen activator inhibitor-1
[PAI-1], TAFI) of fibrinolysis are released.16 Indeed, high levels of PAI-1 precede DIC and
predict poor outcomes.17 Fibrinolysis cannot keep pace with increased fibrin formation,
eventually resulting in under-opposed fibrin deposition in the vasculature.

Inflammatory and coagulation pathways interact in substantial ways. Many of the activated
coagulation factors produced in DIC contribute to the propagation of inflammation by
stimulating endothelial cell release of proinflammatory cytokines. Factor Xa, thrombin, and the
tissue factor-VIIa complex have each been demonstrated to elicit proinflammatory
action. Furthermore, given the anti-inflammatory action of activated protein C and AT, their
impairment in DIC contributes to further dysregulation of inflammation.7,18,19

Components of DIC include the following9 :

• Exposure of blood to procoagulant substances

• Fibrin deposition in the microvasculature
• Impaired fibrinolysis
• Depletion of coagulation factors and platelets (consumptive coagulopathy)
• Organ damage and failure

Frequency

United States

Approximately 18,000 cases of DIC occurred in 1994. DIC may occur in 30-50% of patients
with sepsis.

Mortality/Morbidity

Morbidity and mortality depend on both the underlying disease and the severity of coagulopathy.
Assigning a numerical figure for DIC-specific morbidity and mortality is difficult. Below are
examples of mortality rates in diseases complicated by DIC:

• Idiopathic purpura fulminans associated with DIC has a mortality rate of 18%.
• Septic abortion with clostridial infection and shock associated with severe DIC
has a mortality rate of 50%.
• In the setting of major trauma, the presence of DIC approximately doubles
the mortality rate.3,4

Sex

Incidence is equal in males and females.

Age

No age predilection is known.

Clinical
History

In addition to the symptoms related to the underlying disease process, typically, a history of
blood loss and hypovolemia, such as gastrointestinal bleeding, is present. Look for symptoms
and signs of thrombosis in large vessels, such as deep venous thrombosis (DVT), and of
microvascular thrombosis, such as renal failure. Bleeding from at least 3 unrelated sites is
particularly suggestive of DIC.

• Epistaxis
• Gingival bleeding
• Mucosal bleeding
• Cough
• Dyspnea
• Confusion, disorientation
• Fever

Table 1. Main Features of DIC in a Series of 118 Patients20

Open table in new window

[ CLOSE WINDOW ]

Table
Features Affected
Patients, %

Bleeding 64%

Renal dysfunction 25%

Hepatic dysfunction 19%

Respiratory dysfunction 16%

Shock 14%

Central nervous system

2%
dysfunction

Features Affected
Patients, %

Bleeding 64%

Renal dysfunction 25%

Hepatic dysfunction 19%

Respiratory dysfunction 16%

Shock 14%

Central nervous system

2%
dysfunction

Physical

• Circulation
o Signs of spontaneous and life-threatening hemorrhage
o Signs of subacute bleeding
o Signs of diffuse or localized thrombosis
• Central nervous system
o Nonspecific altered consciousness/stupor
o Focal deficits not usually present
• Cardiovascular system
o Hypotension
o Tachycardia
o Circulatory collapse
• Respiratory system
o Pleural friction rub
o Signs of adult respiratory distress syndrome (ARDS)
• Gastrointestinal system
o Hematemesis
o Hematochezia
• Genitourinary system
o Signs of azotemia and renal failure
o Acidosis
o Hematuria
o Oliguria
o Metrorrhagia
o Uterine hemorrhage
• Dermatologic system
o Petechiae
o Purpura
o Hemorrhagic bullae
o Acral cyanosis
o Skin necrosis of lower limbs (purpura fulminans)
o Localized infarction and gangrene
o Wound bleeding and deep subcutaneous hematomas
o Thrombosis

Causes
Causes of DIC can be classified as acute or chronic, systemic or localized. DIC may be the result
of a single or multiple conditions.

• Acute DIC
o Infectious
 Bacterial (eg, gram-negative sepsis, gram-positive infections,
rickettsial)
 Viral (eg, HIV, cytomegalovirus [CMV], varicella, hepatitis)
 Fungal (eg, Histoplasma)
 Parasitic (eg, malaria)
o Malignancy
 Hematologic (eg, acute myelocytic leukemias)
 Metastatic (eg, mucin-secreting adenocarcinomas)
o Obstetric
 Placental abruption
 Amniotic fluid embolism
 Acute fatty liver of pregnancy
 Eclampsia
o Trauma
o Burns
o Motor vehicle accidents (MVAs)
o Snake envenomation
o Transfusion
o Hemolytic reactions
o Massive transfusion
o Liver disease - Acute hepatic failure
o Prosthetic devices
o Shunts (Denver, LeVeen)
o Ventricular assist devices
• Chronic DIC
o Malignancies
 Solid tumors
 Leukemia
o Obstetric
 Retained dead fetus syndrome
 Retained products of conception
o Hematologic
 Myeloproliferative syndromes
 Paroxysmal nocturnal hemoglobinuria
o Vascular
 Rheumatoid arthritis
 Raynaud disease
o Cardiovascular - Myocardial infarction
o Inflammatory
 Ulcerative colitis
 Crohn disease
 Sarcoidosis
• Localized DIC
o Aortic aneurysms
 o Giant hemangiomas (Kasabach-Merritt syndrome)
o Acute renal allograft rejection
o Hemolytic uremic syndrome

Medication
Therapy should be based on etiology and aimed at eliminating the underlying disease. Therapy
should be appropriately aggressive for the patient's age, disease, and severity and location of
hemorrhage/thrombosis. Treatment for acute DIC includes anticoagulants, blood components,
and antifibrinolytics.

Hemostatic and coagulation parameters should be monitored continuously during treatment.

Base therapeutic decisions on clinical and laboratory evaluation of hemostasis. In cases of low-
grade DIC, therapy other than supportive care may not be warranted or may include antiplatelet
agents or subcutaneous heparin; treatment decisions should be based on clinical and laboratory
evaluation of hemostasis. Activated human protein C has been shown to reduce the rate of
mortality in the setting of severe sepsis for patients at high risk for death; this should be used
cautiously and appropriately, following guidelines for administration.

Anticoagulant agents

These agents are used in the treatment of clinically evident intravascular thrombosis when the
patient continues to bleed or clot 4-6 h after initiation of primary and supportive therapy.
Thrombosis can present as purpura fulminans or acral ischemia. Take special precaution in
obstetric emergencies or massive liver failure. The anti-inflammatory properties of antithrombin
III may be particularly useful in DIC secondary to sepsis.

Heparin

Use and dose of heparin is based on severity of DIC, underlying cause, and extent of thrombosis.
Monitoring results of therapy is mandatory. Heparin augments antithrombin III activity and
prevents conversion of fibrinogen to fibrin. Does not actively lyse but inhibits further
thrombogenesis. Prevents reaccumulation of a clot after spontaneous fibrinolysis.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

80-100 U/kg SC q4-6h or 20,000-30,000 U/d IV continuous infusion

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin,
dextran, dipyridamole, and hydroxychloroquine may increase toxicity

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; subacute bacterial endocarditis; active bleeding; history of

heparin-induced thrombocytopenia

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus

Precautions

Monitor for localized bleeding or hematoma; may aggravate hemorrhage; in neonates,

preservative-free heparin is recommended to avoid possible toxicity (gasping syndrome) by
benzyl alcohol, which is used as preservative; caution in severe hypotension and shock

Antithrombin III (ATnativ, Thrombate III)

Used for moderately severe–to– severe DIC or when levels are depressed markedly. Alpha 2-
globulin that inactivates thrombin, plasmin, and other serine proteases of coagulation, including
factors IXa, Xa, XIa, XIIa, and VIIa. These effects inhibit coagulation.

• Dosing
• Interactions
• Contraindications
 • Precautions

Adult

Total Units = (Desired Level - Initial Level) (0.6 X Total Body Weight kg) IV q8h with a desired
level >125% or loading dose of 100 U/kg IV over 3 h; followed by continuous infusion of 100
U/kg/d

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Increases anticoagulation effects of heparin

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus

Precautions

Caution in hypotension; despite measures taken to delete infectious agents from human product,
potentially still can transmit disease or contain unknown infectious agents

Recombinant human activated protein C

These agents inhibit factors Va and VIIIa of the coagulation cascade. They may also inhibit
plasminogen activator inhibitor-1 (PAI-1).
Drotrecogin alfa-activated (Xigris)

Indicated for reduction of mortality in patients with severe sepsis associated with acute organ
dysfunction and at high risk of death. Recombinant form of human activated protein C that exerts
antithrombotic effect by inhibiting factors Va and VIIIa. Has indirect profibrinolytic activity by
inhibiting PAI-1 and limiting formation of activated thrombin-activatable-fibrinolysis-inhibitor.
May exert anti-inflammatory effect by inhibiting human tumor necrosis factor (TNF) production
by monocytes, blocking leukocyte adhesion to selectins, and limiting thrombin-induced
inflammatory responses within microvascular endothelium.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

24 mcg/kg/h IV by continuous infusion over 96 h

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

None reported; coadministration with drugs that affect hemostasis may increase risk of bleeding
(eg, warfarin, heparin, thrombolytics, glycoprotein IIb/IIIa inhibitors)

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; increased risk of bleeding (eg, active internal bleeding, recent
hemorrhagic stroke, recent intraspinal or intracranial surgery, recent or current trauma, presence
of epidural catheter, intracranial neoplasm, cerebral herniation, severe head trauma)

• Dosing
• Interactions
• Contraindications
• Precautions
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus

Precautions

Bleeding is most common serious adverse effect; caution with conditions that increase risk of
bleeding including INR >3, concurrent therapeutic heparin (>15 U/kg/h), within 6 wk of GI
bleeding episode, within 3 d of thrombolytic therapy, within 7 d of platelet inhibitors
administration, within 3 mo of ischemic stroke, intracranial arteriovenous malformation or
aneurysm, known bleeding diathesis, chronic severe hepatic disease; stop infusion if clinically
significant bleeding occurs; caution with thrombocytopenia (<50 X 109/L); chronic severe
hepatic disease and known bleeding diathesis not associated with the acute coagulopathy related
to sepsis

Blood components

Blood components are used to correct abnormal hemostatic parameters. These products should
be considered only after initial supportive and anticoagulant therapy. Washed PRBCs and
platelet concentrates are considered safe in uncontrolled DIC. Specialized blood components
(cryoprecipitate, FFP) may interfere with or improve DIC.

Packed red blood cells (PRBCs; washed)

Preferred to whole blood since they limit volume, immune, and storage complications. Obtain
PRBCs after centrifugation of whole blood. Use washed or frozen PRBCs in individuals with
hypersensitivity transfusion reactions.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

1 unit of PRBCs should raise hemoglobin by 1 g/dL or raise hematocrit by 3%

Pediatric

Not established

• Dosing
• Interactions
 • Contraindications
• Precautions

None reported

• Dosing
• Interactions
• Contraindications
• Precautions

Competent adult or legal guardian may refuse blood product; immediate consultation with
hospital ethical and legal staff is mandated

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Use CMV-negative units or filtered ones; transfusion reactions and transmission of blood-borne
pathogens are a concern; benefits should outweigh risks associated with such products

Platelet concentrates (Random or single donor, pheresis units)

Considered safe for use in acute DIC.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

Based on platelet count and clinical situation

Pediatric

Not established

• Dosing
 • Interactions
• Contraindications
• Precautions

None reported

• Dosing
• Interactions
• Contraindications
• Precautions

Competent adult or legal guardian may refuse blood product; immediate consultation with
hospital ethical and legal staff mandated

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Platelets should be CMV-negative or the pheresis units from single donors filtered; benefits
should outweigh risks associated with such products

Fresh frozen plasma (FFP)

This treatment entails removing blood from body, spinning it to separate cells from plasma, and
replacing cells suspended in fresh frozen plasma, albumin, or saline. Contains coagulation
factors as well as protein C and protein S. Can be performed by using either 2 large-bore
peripheral IV sites or multiple lumen central line. Recommended with active bleeding and
fibrinogen <100 mg/dL.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

15-20 mL/kg IV or based on clinical situation

Pediatric

Administer as in adults

• Dosing
• Interactions
• Contraindications
• Precautions

None reported

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Viral contamination and infection are remotely possible but unlikely

Cryoprecipitate or fibrinogen concentrates

Not commonly recommended except when fibrinogen is needed.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

Each bag contains 80-100 U of factor VIII; base administration on fibrinogen levels,
antithrombin III levels, and coagulation parameters
Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

None reported

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; uncontrolled DIC with abnormal antithrombin III levels

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Benefits should outweigh risks associated with transfusion therapy; viral contamination and
infection are remotely possible, although unlikely because of prescreening

Antifibrinolytic agents

These agents are used only after all other therapeutic modalities have been tried and deemed
unsuccessful. Increase in circulating plasmin and laboratory evidence of decreased plasminogen
should be documented. Antifibrinolytics may be useful in cases of DIC secondary to
hyperfibrinolysis associated with acute promyelocytic leukemia and other forms of cancer.

Aminocaproic acid (Amicar)

Inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree,
through antiplasmin activity. Main problem is that thrombi that form during treatment are not
lysed, and clinical significance of reducing bleeding is uncertain.
 • Dosing
• Interactions
• Contraindications
• Precautions

Adult

Load 5-10 g IV slowly; followed by 2-4 g/h IV; not to exceed 30 g/d

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Estrogens may cause increase in clotting factors, leading to hypercoagulable state

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; evidence of active intravascular clotting process; because

aminocaproic acid can be fatal in patients with DIC, important to differentiate between
hyperfibrinolysis and DIC

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus

Precautions

Do not administer unless definite diagnosis of hyperfibrinolysis has been made; caution in
cardiac, hepatic, or renal disease
Tranexamic acid (Cyklokapron)

Used as alternative to aminocaproic acid. Inhibits fibrinolysis by displacing plasminogen from

fibrin.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

Nonstandardized dosing: 25 mg/kg PO tid/qid; 1-2 g IV q8-12h

Pediatric

Not established